Published: 17 October 2023
A cheap and widely available prescription drug can improve symptoms of irritable bowel syndrome (IBS) in patients seen in GP surgeries. Those are the findings of new research funded by the NIHR.
Amitriptyline is commonly used at low doses for a range of health concerns. Results from the ATLANTIS trial found it improves IBS symptoms too.
For the study, GPs prescribed the drug and patients managed their own dose based on the severity of their symptoms. This was done using an adjustment document designed for the trial. Most people with IBS are seen and managed in primary care by their GP. This means the results of this trial are likely to be applicable to many people with the condition.
The results showed that patients taking amitriptyline were almost twice as likely to report an overall improvement in symptoms. This was compared to those taking a placebo. Now the trial team is recommending that GPs support their patients with IBS to use amitriptyline to manage their symptoms. To help with this, it has made the dose adjustment document available for clinicians and patients.
Substantial impact
IBS affects around 1 in 20 people worldwide. It causes abdominal pain and changes to bowel movements. The long-term condition, which has no known cure, fluctuates in severity over time. It can have a substantial impact on quality of life and ability to work and socialise. Most treatments only have a modest effect. People often have ongoing troublesome symptoms.
Amitriptyline belongs to a group of medications called tricyclics. They were originally used at high doses to treat depression. They are now rarely used for this condition as newer treatments have been developed.
Previous small trials of low-dose tricyclic antidepressants for IBS suggested a possible benefit in patients seen in hospital clinics. These patients often have more difficult to treat symptoms. However, this new study is the first randomised controlled trial of low-dose amitriptyline versus a placebo tablet for IBS in primary care. It is also the largest trial of amitriptyline for IBS undertaken worldwide.
Clear benefit
GPs already prescribe low-dose amitriptyline to treat chronic nerve and back pain. It is also used to help prevent migraine attacks. NICE guidelines currently state that GPs could consider using a low dose tricyclic, like amitriptyline, for IBS. Until now though, the evidence for a benefit has been uncertain.
Based on the results of the trial, which showed a clear benefit of amitriptyline, GPs can offer low-dose amitriptyline to people with IBS as part of shared decision making. This is if symptoms don't improve with first-line treatments.
Co-chief Investigator Alexander Ford, Professor of Gastroenterology in the University of Leeds’s School of Medicine, said: “Amitriptyline is an effective treatment for IBS and is safe and well tolerated. This new rigorously conducted research indicates that general practitioners should support patients in primary care to try low-dose amitriptyline if their IBS symptoms haven’t improved with recommended first-line treatments.”
Some 463 people with IBS took part in the trial from 3 regions across the UK. They were recruited from 55 general practices in West Yorkshire, Wessex, and West of England.
Participants were put at random into 2 groups. Those receiving amitriptyline and those receiving a placebo. Participants controlled how many tablets of the trial medication they took. They received support via the patient dose adjustment document developed especially for this trial. This enabled participants to increase or decrease the number of tablets. The adjustments were based on their IBS symptoms and any side effects experienced.
Bigger improvement
Participants taking amitriptyline reported a bigger improvement in their symptom scores after 6 months compared with those taking a placebo. Those taking amitriptyline were almost twice as likely as those taking a placebo to report an overall improvement in IBS symptoms. Amitriptyline performed better across a wide range of IBS symptom measures.
Researchers also found participants’ anxiety or depression scores were unaltered. This suggests the beneficial effects of the medication were via the gut, not because of any effect as an antidepressant. No safety concerns were identified.
Professor Andrew Farmer, Director of NIHR's Health Technology Assessment (HTA) Programme, said: "The results of this study are hugely encouraging. It shows that a drug already widely available to treat a number of other conditions appears to be safe and effective for people with IBS. The findings the research team have shared around the adjustment of dosages can be tremendously helpful to GPs in guiding them when treating patients.
“IBS affects a significant number of people in the UK and can have a debilitating effect on their day-to-day lives. This is another excellent example of how high-quality research can lead to positive changes in health and social care practice and treatments for the benefit of patients and healthcare professionals.”
The full results of the study have been published in The Lancet. The researcher team has also presented its findings at UEG Week 2023.
The study was led by researchers at the Universities of Leeds, Southampton, and Bristol. It was funded by the NIHR’s Health Technology Assessment (HTA) Programme. For more information, please visit the study’s Funding and Awards page.